Direct minisci-type C−H amidation of purine bases David Mooney 1 , Peter R. Moore 2 , Ai-Lan Lee 1 1 Institute of Chemical Sciences, Heriot-Watt University, Edinburgh, UK, 2 Early Chemical Development, Pharmaceutical Sciences, AstraZeneca, UK
Purines are one of the most widely occurring N -heterocycles in nature. 1 As well as forming the building blocks for DNA and RNA, they are also significant components of important biomolecules such as ATP, GTP, cAMP, CoA, and NADH. 1 Purine bases are therefore unsurprisingly prevalent in biological and pharmaceutical applications (Figure 1). The ability to directly and selectively C-H functionalise these purine motifs would therefore be highly advantageous.
Figure 1: Examples of Purines Found in Nature and Purine Drugs We present the first method for direct C-H amidation of purine bases for the functionalisation of a wide range of xanthine, adenine and guanine structures, including nucleosides and many well-known drug molecules (Scheme 1). 2 The protocol is capable of installing primary, secondary, as well as tertiary amides. Our variation of the Minisci reaction also has the advantage of being metal-, catalyst- and light-free, thus rendering it cheap, operationally simple, and scalable. 3, 4 By virtue of the tolerance of this protocol to many functional groups, we were also able to demonstrate further modifications of the amidated purine products.
Scheme 1: Minisci Amidation of Purines Protocol 2 References 1. H. Rosemeyer, Chem. Biodivers. , 2004, 1 , 361-401. 2. D. T. Mooney, P. R. Moore and A.-L. Lee, Org. Lett. , 2022, 24 , 8008-8013. 3. D. T. Mooney, B. D. T. Donkin, N. Demirel, P. R. Moore and A.-L. Lee, J. Org. Chem , 2021, 86 , 17282-17293. 4. E. B. McLean, D. T. Mooney, D. J. Burns and A.-L. Lee, Org. Lett. , 2022, 24 , 686-691.
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© The Author(s), 2023
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